The purpose of this proposal is to study the direct effects of neutrotransmitter on the release of B-endorphin-related peptides from hypothalamic neurons in culture. Fetal rat hypothalami will be dissected under sterile conditions and cultured in hormone or serum-supplemented Dulbecco Modified Eagle's Medium. Different biologically active neurotransmitters and related compounds will be added to the medium and the dose-response and time-course effects of these treatments on B-endorphin release will be determined. The agents to be investigated will evaluate five types of brain neurotransmitter receptors: (1) dopamine; (2) norepinephrine; (3) serotonin; (4) acetylcholine; and (5) opiate receptors. Further, the different molecular forms of B-endorphin released by the cell cultures will be identified and quantified by cation exchange chromatography in combination with immunoassay. Results of these experiments should help to elucidate the control of B-endorphin peptides in brain and hopefully will increase our understanding of the mechanisms by which these agents influence analgesia.